Delta9-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC plasma pharmacokinetics during and after continuous high-dose oral THC

Clin Chem. 2009 Dec;55(12):2180-9. doi: 10.1373/clinchem.2008.122119. Epub 2009 Oct 15.


Background: Delta(9)-tetrahydrocannabinol (THC) is the primary psychoactive constituent of cannabis and an active cannabinoid pharmacotherapy component. No plasma pharmacokinetic data after repeated oral THC administration are available.

Methods: Six adult male daily cannabis smokers resided on a closed clinical research unit. Oral THC capsules (20 mg) were administered every 4-8 h in escalating total daily doses (40-120 mg) for 7 days. Free and glucuronidated plasma THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH) were quantified by 2-dimensional GC-MS during and after dosing.

Results: Free plasma THC, 11-OH-THC, and THCCOOH concentrations 19.5 h after admission (before controlled oral THC dosing) were mean 4.3 (SE 1.1), 1.3 (0.5), and 34.0 (8.4) microg/L, respectively. During oral dosing, free 11-OH-THC and THCCOOH increased steadily, whereas THC did not. Mean peak plasma free THC, 11-OH-THC, and THCCOOH concentrations were 3.8 (0.5), 3.0 (0.7), and 196.9 (39.9) mug/L, respectively, 22.5 h after the last dose. Escherichia coli beta-glucuronidase hydrolysis of 264 cannabinoid specimens yielded statistically significant increases in THC, 11-OH-THC, and THCCOOH concentrations (P < 0.001), but conjugated concentrations were underestimated owing to incomplete enzymatic hydrolysis.

Conclusions: Plasma THC concentrations remained >1 mug/L for at least 1 day after daily cannabis smoking and also after cessation of multiple oral THC doses. We report for the first time free plasma THC concentrations after multiple high-dose oral THC throughout the day and night, and after Escherichia coli beta-glucuronidase hydrolysis. These data will aid in the interpretation of plasma THC concentrations after multiple oral doses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Dronabinol / administration & dosage
  • Dronabinol / analogs & derivatives*
  • Dronabinol / blood
  • Dronabinol / pharmacokinetics*
  • Escherichia coli / enzymology
  • Gas Chromatography-Mass Spectrometry
  • Glucuronidase / metabolism
  • Humans
  • Hydrolysis
  • Male
  • Middle Aged
  • Young Adult


  • 11-hydroxy-delta(9)-tetrahydrocannabinol
  • 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid
  • Dronabinol
  • Glucuronidase